Project Summary/Abstract The brain neuropeptides oxytocin (OT) and arginine vasopressin (AVP) play important roles in altering neural circuits that regulate social behavior. These ligands regulate normative social function in a host of areas, including social attachment, parental behavior, aggression, and complex social cognition. In pathological brain/behavior conditions, many disorders are characterized by dramatic deficits in the social realm. Knowledge of the way OT and AVP alter cellular function in neurons has the potential to both identify mechanisms that produce social dysfunction and to design compounds that normalize cellular function and behavior. The present project takes advantage of the discovery of novel OT ligand structure, and variation in cellular receptors for OT and AVP in the marmoset, a species that exhibits social monogamy, infant care by males, and a family-like social structure. The first aim will characterize the effects of ligand diversity on the alteration of behavior in a variety of social domains by using in vivo behavioral pharmacology. These domains include male-female attachment, infant care, mate-defense aggression, and social cooperation/altruism. The second aim will quantify the receptor pharmacology and binding characteristics of the ligand variants with the cell membrane G protein-coupled receptors for these related ligands. The final aim will define the specific modifications in G protein-mediated cell signaling processes brought about by these ligands to determine if ligand variation that modifies social behavior does so through specific or `biased' activation of different signaling pathways. Collectively, these three aims will provide important insights into the ways in which neurons and behavior are modified by OT and AVP ligand variants, leading to enhanced knowledge of the neurobiology of social behavior. The project can point to potential options for designing neuropeptide ligand- receptor complexes that could serve as effective tools to treat social dysfunction.